Pleiotropic Effects of Simvastatin on Wound Healing in Diabetic Mice

To evaluate the effects of pre-treatment with low-dose simvastatin on angiogenesis and wound healing in a diabetic mouse model.

Balb/c nude mice were divided into three groups, including control (CON), diabetic (DM, and diabetic pre-treated with low-dose simvastatin (DM+ SIM). Seven days prior to wounding, the DM + SIM group was started on oral simvastatin (0.25 mg/kg/day). Eleven weeks after diabetes was induced, all mice were subjected to a bilateral full-thickness excisional skin wound on the back (0.6 x 0.6 cm²). On day 14 after wounding, percentage of wound closure (%WC), percentage of capillary vascularity (%CV), and neutrophil infiltration were determined using Image Pro-Plus, confocal fluorescence microscopy, and hematoxylin and eosin (H&E) staining, respectively. Tissue vascular endothelial growth factor (VEGF) was detected by ELISA at days 7 and 14, post-wounding.

On day 14, %WC and %CV in CON and DM + SIM groups were significantly increased, with no significant change observed in the DM group. Neutrophil infiltration in the CON and DM + SIM groups was signficantly lower than that of the DM group. VEGF levels in the CON and DM + SIM groups were significantly higher than levels in the DM group on day 7, but not different among groups on day 14.

The present study demonstrated that pre-treatment with low-dose simvastatin could increase angiogenesis, reduce inflammation, and improve wound healing in diabetic mice.